DSM-IV › Substance-related disorders › Substance-induced disorders › Substance withdrawal 

Substance Withdrawal

Diagnostic Features

The essential feature of Substance Withdrawal is the development of a substance-specific maladaptive behavioral change, with physiological and cognitive concomitants, that is due to the cessation of, or reduction in, heavy and prolonged substance use (Criterion A). The substance-specific syndrome causes clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion B). The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder (Criterion C). Withdrawal is usually, but not always, associated with Substance Dependence (see p. 192). Most (perhaps all) individuals with Withdrawal have a craving to readminister the substance to reduce the symptoms. The diagnosis of Withdrawal is recognized for the following groups of substances: alcohol; amphetamines and other related substances; cocaine; nicotine; opioids; and sedatives, hypnotics, or anxiolytics. The signs and symptoms of Withdrawal vary according to the substance used, with most symptoms being the opposite of those observed in Intoxication with the same substance. The dose and duration of use and other factors such as the presence or absence of additional illnesses also affect withdrawal symptoms. Withdrawal develops when doses are reduced or stopped, whereas signs and symptoms of Intoxication improve (gradually in some cases) after dosing stops.

Criteria for Substance Withdrawal

1. The development of a substance-specific syndrome due to the cessation of (or reduction in) substance use that has been heavy and prolonged.
2. The substance-specific syndrome causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
3. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

Associated Features of Substance Dependence, Abuse, Intoxication, and Withdrawal

Assessment issues.

The diagnosis of Substance Dependence requires obtaining a detailed history from the individual and, whenever possible, from additional sources of information (e.g., medical records; a spouse, relative, or close friend). In addition, physical examination findings and laboratory test results can be helpful.

Route of administration.

The route of administration of a substance is an important factor in determining its effects (including the time course of developing Intoxication, the probability that its use will produce physiological changes associated with Withdrawal, and the likelihood that use will lead to Dependence or Abuse). Routes of administration that produce more rapid and efficient absorption into the bloodstream (e.g., intravenous, smoking, or "snorting") tend to result in a more intense intoxication and an increased likelihood of an escalating pattern of substance use leading to Dependence. These routes of administration quickly deliver a large amount of the substance to the brain and, thus, are associated with higher levels of substance consumption and an increased likelihood of toxic effects. For example, a person who uses intravenous amphetamine is more likely to rapidly consume large amounts of the substance and thereby risk an overdose than the person who only takes amphetamine orally.

Speed of onset within a class of substance.

Rapidly acting substances are more likely than slower-acting substances to produce immediate intoxication and lead to Dependence or Abuse. For example, because diazepam and alprazolam both have a more rapid onset than phenobarbital, they may consequently be more likely to lead to Substance Dependence or Abuse.

Duration of effects.

The duration of effects associated with a particular substance is also important in determining the time course of Intoxication and whether use of the substance will lead to Dependence or Abuse. Relatively short-acting substances (e.g., certain anxiolytics) tend to have a higher potential for the development of Dependence or Abuse than substances with similar effects that have a longer duration of action (e.g., phenobarbital). The half-life of the substance parallels aspects of Withdrawal: the longer the duration of action, the longer the time between cessation and the onset of withdrawal symptoms and the longer the Withdrawal is likely to last. For example, for heroin, the onset of acute withdrawal symptoms is more rapid but the withdrawal syndrome is less persistent than for methadone. In general, the longer the acute withdrawal period, the less intense the syndrome tends to be.

Use of multiple substances.

Substance Dependence, Abuse, Intoxication, and Withdrawal often involve several substances used simultaneously or sequentially. For example, individuals with Cocaine Dependence frequently also use alcohol, anxiolytics, or opioids, often to counteract lingering cocaine-induced anxiety symptoms. Similarly, individuals with Opioid Dependence or Cannabis Dependence usually have several other Substance-Related Disorders, most often involving alcohol, anxiolytics, amphetamine, or cocaine. When criteria for more than one Substance-Related Disorder are met, the diagnosis of Polysubstance Dependence should not be used. It applies only to those situations in which the pattern of multiple substance use does not meet the criteria for Dependence or Abuse for any specific substance, but meets it for the group of substances taken as a whole. The situations in which a diagnosis of Polysubstance Dependence should be given are described on p. 293.

Associated laboratory findings.

Laboratory analyses of blood and urine samples can help determine recent use of a substance. Blood concentrations offer additional information on the amount of substance still present in the body. It should be noted that a positive blood or urine test does not by itself indicate that the individual has a pattern of substance use that meets criteria for a Substance-Related Disorder and that a negative blood or urine test does not by itself rule out a diagnosis of a Substance-Related Disorder.

In the case of Intoxication, blood and urine tests can help to determine the relevant substance(s) involved. Specific confirmation of the suspected substance may require toxicological analysis, because various substances have similar Intoxication syndromes; individuals often take a number of different substances; and because substitution and contamination of street drugs are frequent, those who obtain substances illicitly often do not know the specific contents of what they have taken. Toxicological tests may also be helpful in differential diagnosis to determine the role of Substance Intoxication or Withdrawal in the etiology (or exacerbation) of symptoms of a variety of mental disorders (e.g., Mood Disorders, Psychotic Disorders). Furthermore, serial blood levels may help to differentiate Intoxication from Withdrawal.

The blood concentration of a substance may be a useful clue in determining whether the person has a high tolerance to a given group of substances (e.g., a person presenting with a blood alcohol level of over 150 mg/dL without signs of Alcohol Intoxication has a significant tolerance to alcohol and is likely to be a chronic user of either alcohol or a sedative, hypnotic, or anxiolytic). Another method for assessing tolerance is to determine the individual's response to an agonist medication. For example, a person who does not exhibit any signs of intoxication from a dose of pentobarbital of 200 mg or higher has a significant tolerance to sedatives, hypnotics, or anxiolytics and may need treatment to prevent the development of Withdrawal.

Laboratory tests can be useful in identifying Withdrawal in individuals with Substance Dependence. Evidence for cessation or reduction of dosing may be obtained by history or by toxicological analysis of body fluids (e.g., urine or blood). Although many substances and their metabolites clear the urine within 48 hours of ingestion, certain metabolites may be present for a longer period in those who use the substance chronically. If the person presents with Withdrawal from an unknown substance, urine tests may help identify the substance from which the person is withdrawing and make it possible to initiate appropriate treatment. Urine tests may also be helpful in differentiating Withdrawal from other mental disorders, because withdrawal symptoms can mimic the symptoms of mental disorders unrelated to use of a substance. In cases in which Opioid Dependence cannot be clearly confirmed by history, the use of an antagonist (e.g., naloxone) to demonstrate whether withdrawal symptoms are induced may be informative.

Associated physical examination findings and general medical conditions.

As presented in the sections specific to the 11 classes of substance, intoxication and withdrawal states are likely to include physical signs and symptoms that are often the first clue to a substance-related state. In general, intoxication with amphetamines or cocaine is accompanied by increases in blood pressure, respiratory rate, pulse, and body temperature. Intoxication with sedative, hypnotic, or anxiolytic substances or with opioid medication often involves the opposite pattern. Substance Dependence and Abuse are often associated with general medical conditions often related to the toxic effects of the substances on particular organ systems (e.g., cirrhosis in Alcohol Dependence) or the routes of administration (e.g., human immunodeficiency virus [HIV] infection from shared needles).

Associated mental disorders.

Substance use is often a component of the presentation of symptoms of mental disorders. When the symptoms are judged to be a direct physiological consequence of a substance, a Substance-Induced Disorder is diagnosed (see p. 209). Substance-Related Disorders are also commonly comorbid with, and complicate the course and treatment of, many mental disorders (e.g., Conduct Disorder in adolescents; Antisocial and Borderline Personality Disorders, Schizophrenia, Bipolar Disorder).

Recording Procedures for Dependence, Abuse, Intoxication, and Withdrawal

For drugs of abuse.

The clinician should use the code that applies to the class of substances, but record the name of the specific substance rather than the name of the class. For example, the clinician should record 292.0 Secobarbital Withdrawal (rather than Sedative, Hypnotic, or Anxiolytic Withdrawal) or 305.70 Methamphetamine Abuse (rather than Amphetamine Abuse). For substances that do not fit into any of the classes (e.g., amyl nitrite), the appropriate code for "Other Substance Dependence," "Other Substance Abuse," "Other Substance Intoxication," or "Other Substance Withdrawal" should be used and the specific substance indicated (e.g., 305.90 Amyl Nitrite Abuse). If the substance taken by the individual is unknown, the code for the class "Other (or Unknown)" should be used (e.g., 292.89 Unknown Substance Intoxication). For a particular substance, if criteria are met for more than one Substance-Related Disorder, all should be diagnosed (e.g., 292.0 Heroin Withdrawal; 304.00 Heroin Dependence). If there are symptoms or problems associated with a particular substance but criteria are not met for any of the substance-specific disorders, the Not Otherwise Specified category can be used (e.g., 292.9 Cannabis-Related Disorder Not Otherwise Specified). If multiple substances are used, all relevant Substance-Related Disorders should be diagnosed (e.g., 292.89 Mescaline Intoxication; 304.20 Cocaine Dependence). The situations in which a diagnosis of 304.80 Polysubstance Dependence should be given are described on p. 293.

For medications and toxins.

For medications not covered above (as well as for toxins), the code for "Other Substance" should be used. The specific medication can be coded by also listing the appropriate E-code on Axis I (see Appendix G) (e.g., 292.89 Benztropine Intoxication; E941.1 Benztropine). E-codes should also be used for classes of substances listed above when they are taken as prescribed (e.g., opioids).

Specific Culture, Age, and Gender Features

There are wide cultural variations in attitudes toward substance consumption, patterns of substance use, accessibility of substances, physiological reactions to substances, and prevalence of Substance-Related Disorders. Some groups forbid use of alcohol, whereas in others the use of various substances for mood-altering effects is widely accepted. The evaluation of any individual's pattern of substance use must take these factors into account. Patterns of medication use and toxin exposure also vary widely within and between countries.

Individuals between ages 18 and 24 years have relatively high prevalence rates for the use of virtually every substance, including alcohol. For drugs of abuse, Intoxication is usually the initial Substance-Related Disorder and usually begins in the teens. Withdrawal can occur at any age as long as the relevant drug has been taken in high-enough doses over a long-enough period of time. Dependence can also occur at any age, but typically has its initial onset for most drugs of abuse in the 20s, 30s, and 40s. When a Substance-Related Disorder other than Intoxication begins in early adolescence, it is often associated with Conduct Disorder and failure to complete school. For drugs of abuse, Substance-Related Disorders are usually diagnosed more commonly in males than in females, but the sex ratios vary with class of substance.

Course

The course of Dependence, Abuse, Intoxication, and Withdrawal varies with the class of substance, route of administration, and other factors. The "Course" sections for the various classes of substances indicate the specific features characteristic of each. However, some generalizations across substances can be made.

Intoxication usually develops within minutes after a sufficiently large single dose and continues or intensifies with frequently repeated doses. Intoxication begins to abate as blood or tissue concentrations of the substance decline, but signs and symptoms may resolve slowly. The onset of Intoxication may be delayed with slowly absorbed substances or with those that must be metabolized to active compounds. Long-acting substances may produce prolonged intoxications.

Withdrawal develops with the decline of the substance in the central nervous system. Early symptoms of Withdrawal usually develop a few hours after dosing stops for substances with short elimination half-lives (e.g., alcohol, lorazepam, or heroin), although withdrawal seizures may develop several weeks after termination of high doses of long-half-life anxiolytic substances. The more intense signs of Withdrawal usually end within a few days to a few weeks after the cessation of substance use, although some subtle physiological signs may be detectable for many weeks or even months as part of a protracted withdrawal syndrome. For example, impaired sleep can be seen for months after a person with Alcohol Dependence stops drinking.

A diagnosis of Substance Abuse is more likely in individuals who have begun using substances only recently. For many individuals, Substance Abuse with a particular class of substances evolves into Substance Dependence for the same class of substance. This is particularly true for those substances that have a high potential for the development of tolerance, withdrawal, and patterns of compulsive use such as cocaine or heroin. Some individuals have evidence of Substance Abuse that occurs over an extended period of time without ever developing Substance Dependence. This is more true for those substances that have a lower potential for the development of tolerance, withdrawal, and patterns of compulsive use. Once criteria for Substance Dependence are met, a subsequent diagnosis of Substance Abuse cannot be given for any substance in the same class. For a person with Substance Dependence in full remission, any relapses that meet criteria for Substance Abuse would be considered Dependence in partial remission (see course specifiers, p. 195).

The course of Substance Dependence is variable. Although relatively brief and self-limited periods of Dependence may occur (particularly during times of psychosocial stress), the course is usually chronic, lasting years, with periods of exacerbation and partial or full remission. There may be periods of heavy intake and severe problems, periods of total abstinence, and times of nonproblematic use of the substance, sometimes lasting for months. Substance Dependence is sometimes associated with spontaneous, long-term remissions. For example, follow-ups reveal that 20% (or more) of individuals with Alcohol Dependence become permanently abstinent, usually following a severe life stress (e.g., the threat or imposition of social or legal sanctions, discovery of a life-threatening medical complication). During the first 12 months after the onset of remission, the individual is particularly vulnerable to having a relapse. Many individuals underestimate their vulnerability to developing a pattern of Dependence. When in a period of remission, they incorrectly assure themselves that they will have no problem regulating substance use and may experiment with gradually less restrictive rules governing the use of the substance, only to experience a return to Dependence. The presence of co-occurring mental disorders (e.g., Antisocial Personality Disorder, untreated Major Depressive Disorder, Bipolar Disorder) often increases the risk of complications and a poor outcome.

Impairment and Complications

Although many individuals with substance-related problems have good functioning (e.g., in personal relationships, job performance, earning abilities), these disorders often cause marked impairment and severe complications. Individuals with Substance-Related Disorders frequently experience a deterioration in their general health. Malnutrition and other general medical conditions may result from improper diet and inadequate personal hygiene. Intoxication or Withdrawal may be complicated by trauma related to impaired motor coordination or faulty judgment. The materials used to "cut" certain substances can produce toxic or allergic reactions. Using substances intranasally ("snorting") may cause erosion of the nasal septum. Stimulant use can result in sudden death from cardiac arrhythmias, myocardial infarction, a cerebrovascular accident, or respiratory arrest. The use of contaminated needles during intravenous administration of substances can cause human immunodeficiency virus (HIV) infection, hepatitis, tetanus, vasculitis, septicemia, subacute bacterial endocarditis, embolic phenomena, and malaria.

Substance use can be associated with violent or aggressive behavior, which may be manifested by fights or criminal activity, and can result in injury to the person using the substance or to others. Automobile, home, and industrial accidents are a major complication of Substance Intoxication and result in an appreciable rate of morbidity and mortality. Approximately one-half of all highway fatalities involve either a driver or a pedestrian who is intoxicated. In addition, perhaps 10% of individuals with Substance Dependence commit suicide, often in the context of a Substance-Induced Mood Disorder. Finally, because most, if not all, of the substances described in this section cross the placenta, they may have potential adverse effects on the developing fetus (e.g., fetal alcohol syndrome). When taken repeatedly in high doses by the mother, a number of substances (e.g., cocaine, opioids, alcohol, and sedatives, hypnotics, and anxiolytics) are capable of causing physiological dependence in the fetus and a withdrawal syndrome in the newborn.

Familial Pattern

Information about familial associations has been best studied for the Alcohol-Related Disorders (see the detailed discussion on p. 221). There is some evidence for genetically determined differences among individuals in the doses required to produce Alcohol Intoxication. Although Substance Abuse and Dependence appear to aggregate in families, some of this effect may be explained by the concurrent familial distribution of Antisocial Personality Disorder, which may predispose individuals to the development of Substance Abuse or Dependence. Furthermore, the children of individuals with Alcohol Dependence (but not Antisocial Personality Disorder) do not have a predisposition to developing Substance Dependence on all substances; they are only at higher risk for Alcohol Dependence.

Differential Diagnosis

Substance-Related Disorders are distinguished from nonpathological substance use (e.g., "social" drinking) and from the use of medications for appropriate medical purposes by the presence of a pattern of multiple symptoms occurring over an extended period of time (e.g., tolerance, withdrawal, compulsive use) or the presence of substance-related problems (e.g., medical complications, disruption in social and family relationships, vocational or financial difficulties, legal problems). Repeated episodes of Substance Intoxication are almost invariably prominent features of Substance Abuse or Dependence. However, one or more episodes of Intoxication alone are not sufficient for a diagnosis of either Substance Dependence or Abuse.

It may sometimes be difficult to distinguish between Substance Intoxication and Substance Withdrawal. If a symptom arises during the time of dosing and then gradually abates after dosing stops, it is likely to be part of Intoxication. If the symptom arises after stopping the substance, or reducing its use, it is likely to be part of Withdrawal. Individuals with Substance-Related Disorders often take more than one substance and may be intoxicated with one substance (e.g., heroin) while withdrawing from another (e.g., diazepam). This differential is further complicated by the fact that the signs and symptoms of Withdrawal from some substances (e.g., sedatives) may partially mimic Intoxication with others (e.g., amphetamines). Substance Intoxication is differentiated from Substance Intoxication Delirium (p. 143), Substance-Induced Psychotic Disorder, With Onset During Intoxication (p. 338), Substance-Induced Mood Disorder, With Onset During Intoxication (p. 405), Substance-Induced Anxiety Disorder, With Onset During Intoxication (p. 479), Substance-Induced Sexual Dysfunction, With Onset During Intoxication (p. 562), and Substance-Induced Sleep Disorder, With Onset During Intoxication (p. 655), by the fact that the symptoms in these latter disorders are in excess of those usually associated with Substance Intoxication and are severe enough to warrant independent clinical attention. Substance Withdrawal is distinguished from Substance Withdrawal Delirium (p. 143), Substance-Induced Psychotic Disorder, With Onset During Withdrawal (p. 338), Substance-Induced Mood Disorder, With Onset During Withdrawal (p. 405), Substance-Induced Anxiety Disorder, With Onset During Withdrawal (p. 479), and Substance-Induced Sleep Disorder, With Onset During Withdrawal (p. 655), by the fact that the symptoms in these latter disorders are in excess of those usually associated with Substance Withdrawal and are severe enough to warrant independent clinical attention.

The additional Substance-Induced Disorders described above present with symptoms that resemble non-substance-induced (i.e., primary) mental disorders. See p. 210 for a discussion of this important differential diagnosis.

An additional diagnosis of a Substance-Induced Disorder is usually not made when symptoms of preexisting mental disorders are exacerbated by Substance Intoxication or Substance Withdrawal (although a diagnosis of Substance Intoxication or Withdrawal might be appropriate). For example, Intoxication with some substances may exacerbate the mood swings in Bipolar Disorder, the auditory hallucinations and paranoid delusions in Schizophrenia, the intrusive thoughts and terrifying dreams in Posttraumatic Stress Disorder, and the anxiety symptoms in Panic Disorder, Generalized Anxiety Disorder, Social Phobia, and Agoraphobia. Intoxication or Withdrawal may also increase the risk of suicide, violence, and impulsive behavior in individuals with a preexisting Antisocial or Borderline Personality Disorder.

Many neurological (e.g., head injuries) or metabolic conditions produce symptoms that resemble, and are sometimes misattributed to, Intoxication or Withdrawal (e.g., fluctuating levels of consciousness, slurred speech, incoordination). The symptoms of infectious diseases may also resemble Withdrawal from some substances (e.g., viral gastroenteritis can be similar to Opioid Withdrawal). If the symptoms are judged to be a direct physiological consequence of a general medical condition, the appropriate Mental Disorder Due to a General Medical Condition should be diagnosed. If the symptoms are judged to be a direct physiological consequence of both substance use and a general medical condition, both a Substance-Related Disorder and a Mental Disorder Due to a General Medical Condition may be diagnosed. If the clinician is unable to determine whether the presenting symptoms are substance induced, due to a general medical condition, or primary, the appropriate Not Otherwise Specified Category should be diagnosed (e.g., psychotic symptoms with indeterminate etiology would be diagnosed as Psychotic Disorder Not Otherwise Specified).

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision^TM. Copyright 2000 American Psychiatric Association. All Rights Reserved.